The long term aim of this project is to delineate the mechanisms of deranged renal function which result from or contribute to the pathophysiology of hypertension. This project will utilize models of two-kidney, one artery stenosis and one-kidney, one artery stenosis hypertension in Sprague-Dawley and Munich-Wistar rats which will allow us to define the mechanisms of altered function of these kidneys at the level of the single nephron and at the glomerulus. These models offer the advantage of allowing assessment of varying influences of angiotensin on single nephron function simultaneously in settings of elevated renal perfusion pressure (nonclipped side kidney) and in settings of normal perfusion pressure (clipped side kidney) as temporally related to the development of systemic hypertension. The general hypothesis which we will explore is that alterations in tubuloglomerular feedback activity contribute importantly to the participation of the kidney in the development and early maintenance phases of hypertension by perturbing renal hemodynamic function. The focus of this project is (1) to elucidate the quantitative contribution of altered tubuloglomerular feedback activity to the altered function of the single nephron in these kidneys and (2) to determine how these intrarenal alterations of single nephron hemodynamic function contributes to the development and maintenance of the renal vascular hypertension. (1) The initial studied will assess the quantitative contributions of altered tubuloglomerular feedback activity to the control of hydrostatic pressure and single nephron plasma flow in the glomerular capillary. (2) Other experiments will delineate the contribution of altered tubuloglomerular feedback activity to the angiotensin dependent development phases of hypertension in these models chronologically. (3) We will test the hypothesis that the mechanism of acute renal dysfunction observed in 1-K, 1C hypertensive rats in response to blockade of converting enzyme activity is the result of altered angiotensin influences on tubuloglomerular feedback activity; and (4) test the hypothesis that angiotensin mediated alterations of tubule absorption contributes directly to the alterations of tubuloglomerular feedback activity in the nonclipped kidney and in the clipped kidneys of hypertensive rats.